Transposon mutagenesis identifies genes driving hepatocellular carcinoma in a chronic hepatitis B mouse model

Emilie A. Bard-Chapeau, Anh Tuan Nguyen, Alistair G. Rust, Ahmed Sayadi, Philip Lee, Belinda Q. Chua, Lee Sun New, Johann De Jong, Jerrold M. Ward, Christopher K Y Chin, Valerie Chew, Han Chong Toh, Jean Pierre Abastado, Touati Benoukraf, Richie Soong, Frederic A. Bard, Adam J. Dupuy, Randy L. Johnson, George K. Radda, Eric Chun Yong ChanLodewyk F A Wessels, David J. Adams, Nancy A. Jenkins, Neal G. Copeland

Research output: Contribution to journalArticle

75 Scopus citations

Abstract

The most common risk factor for developing hepatocellular carcinoma (HCC) is chronic infection with hepatitis B virus (HBV). To better understand the evolutionary forces driving HCC, we performed a near-saturating transposon mutagenesis screen in a mouse HBV model of HCC. This screen identified 21 candidate early stage drivers and a very large number (2,860) of candidate later stage drivers that were enriched for genes that are mutated, deregulated or functioning in signaling pathways important for human HCC, with a striking 1,199 genes being linked to cellular metabolic processes. Our study provides a comprehensive overview of the genetic landscape of HCC.

Original languageEnglish (US)
Pages (from-to)24-32
Number of pages9
JournalNature Genetics
Volume46
Issue number1
DOIs
StatePublished - Jan 2014

ASJC Scopus subject areas

  • Genetics

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